#MS-Selfie: infections and how to self-manage your bladder

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In response to a comment from one of our readers, I am starting a series of posts called #MS-Selfie, which is derived from the term self-management. These posts are a long read but will help you manage your own MS.

Over the last few weeks, many of my posts have focused on MS-specific mechanisms underlying why pwMS become disabled and how DMTs can delay, or prevent, this damage from occurring. The message as always is to treat early and effectively, and if you want the best chance of doing well over your lifetime you need to consider flipping the pyramid and going for high-efficacy DMTs. I have also highlighted subtle, but potentially important differences, between the non-selective immune reconstitution therapies (NIRTs) and the more selective immune reconstitution therapies (SIRTs) and maintenance therapies in terms of their impact on end-organ damage markers and disability improvement. These two will almost certainly become more important as a treatment target in the next decade.

You may or may not know about Sir Dave Brailsford and his philosophy of marginal gains. Sir Dave applied a theory of marginal gains to cycling; he proposed that if the British team broke down everything they could think of that goes into competing on a bike, and then improved each element by 1%, they would achieve a significant aggregated increase in performance. He got the British Cycling to adopt this and the rest is history. Britain dominates the World Championships, Olympic Games, Paralympics and now the Tour de France with Team Sky. So what this got to do with MS?

If we approached the management of MS in the same way, we will almost certainly improve the outcome of British people living with MS. To optimise your outcome it is not good enough just to focus on MS DMTs, but all the factors that could worsen or improve your MS.

This is post is about one of these factors infections and bladder dysfunction.

Relapses and infections

Infections, in particular, viral infections, are a known trigger of relapse. You are more than twice as likely to have a relapse in the week prior to, or the 5 weeks after, an infection. In the study below infections in this paper were mainly symptomatic upper respiratory infections due to viruses, so the risk may be much higher if we could also count hidden or asymptomatic infections.

What do I mean by asymptomatic infections? We are continuously being exposed to new viruses that infect us but don’t necessarily cause symptoms. An example of this is the JC virus that causes PML (progressive multifocal leukoencephalopathy). When we initially become infected with the JC virus it does not cause any symptoms; it simply gets into our body and persists. It persists as an asymptomatic lytic infection. In the majority of us, persistent JC virus infection doesn’t cause any problems. Only if we become immunocompromised do we have a chance of this virus mutating and causing PML. Similarly, for the majority of us when we get infected with Epstein-Barr virus (EBV) it does not cause symptoms; only the minority of us get glandular fever or infectious mononucleosis. The same applies to another herpes virus called CMV or cytomegalovirus; asymptomatic infection is the rule. What is interesting about the herpes viruses is that they become latent in the body and reactivate every now and then. These reactivations of latent viruses are usually asymptomatic but are strong enough to stimulate the immune system and may trigger relapses. In fact, there is some evidence that this may actually be the case.

When I did my PhD I studied a marker of immune activation on a daily basis in pwMS over many months. I found that immune activation usually preceded the occurrence of new MRI lesions by a few weeks. Please remember new MRI lesions are the equivalent of subclinical relapses. I, therefore, proposed in my thesis that latent viral reactivations may be the factor responsible for this immune activation, which then triggers MS disease activity. This is one of the reasons why I am so interested in the viral MS hypothesis. Virus-induced MS exacerbations don’t have to apply to exogenous viruses only, i.e. viruses that come from outside the body but could also apply to endogenous viruses, i.e. viruses that reside in our bodies or genome. The latter refers to human endogenous retroviruses (HERVs). This is one of the hypotheses that underpins our Charcot Project. Can we treat MS by reducing endogenous viral reactivation (HERVs)? Can we treat MS by preventing reactivation of latent herpes viruses, in particular, EBV? This is why we are exploring add-on antiviral studies to see if we can prevent MS disease reactivation.

It is very difficult to avoid viral infections. The one thing you can do is have your annual flu vaccine and try to avoid coming into contact with people who are clearly ill and potentially shedding virus.  

Please, note that the observation of infections triggering relapses is not limited to viral infections, but also applies to bacterial infections, in particular, urinary tract infections. This is why we have to improve the management of bladder problems in pwMS with the aim of preventing or reducing urinary tract infections (UTIs). PwMS with recurrent UTIs do worse than pwMS without UTIs. However, to prevent or reduce the frequency of UTIs you have to know how MS causes bladder problems and to deal with them.  

Bladder dysfunction

Bladder dysfunction is the most common symptomatic problem I have to deal with in the clinic. More than 50% of pwMS have bladder problems. Bladder dysfunction in pwMS is one of the integrators of early damage, particularly spinal cord damage, and an early read-out of a poor prognosis. I, therefore, take symptoms of bladder problems seriously as it has implications around MS prognosis and its treatment. For example, if you have early bladder symptoms may choose a more effective therapy early on rather than take chance on a lower efficacy DMT waiting to see if you are a responder or not.

Why do pwMS who develop bladder dysfunction do worse than those who don’t have bladder symptoms? The bladder is a complicated organ with several neurological components that can be affected by MS and hence is sensitive to damage. The descending nerve fibres that travel from the brain to the lower spinal segments are very long and hence have a greater chance of being affected by MS lesions in their path to the bladder centre in the lower spinal cord. The same is true for motor fibres that control movement in the lower legs. The bladder, unlike the motor fibres to the leg, is more complicated because of the need to coordinate the different muscles. Therefore any progressive MS damage is more likely to manifest with bladder dysfunction early on. This is why I now include bladder problems in my list of poor prognostic factors in MS.

The bladder has two muscles that need to be coordinated in their action for the bladder to function normally. The detrusor or balloon muscle and the sphincter or valve muscles When the bladder is filling up the detrusor muscle has to relax to allow the bladder to expand with urine and the sphincter has to contract to keep the urine in the bladder. The opposite occurs when you pass urine; the sphincter or valve opens and the detrusor contracts to empty the bladder.

Hesitancy

What happens if the two muscles are not coordinated? This causes the symptom of hesitancy, i.e. when you try and pass urine the sphincter won’t open and you have to wait for the bladder to open; pwMS find this very frustrating. The sphincter can also close as you passing urine, which breaks up the urine stream or prevents you from emptying your bladder completely. The latter also causes dribbling. The medical term for incoordination of the bladder muscles is dyssynergia or more correctly detrusor-sphincter-dyssynergia (DSD). The drug treatment for DSD includes the so-called alpha-blockers ( prazosin, indoramin, tamsulosin, alfuzosin, doxazosin and terazosin). Other strategies include small bladder stimulators or vibrators; these are placed over the pubic area and work by blocking signals that inhibit the sphincters. The vibrators work in some pwMS and may help relax the sphincter. It is also important to try and relax when passing urine; this often helps improve hesitancy. The sound of running water, for example from a tap, may trigger the relaxation of the sphincter. This can be a problem in public toilets when opening a nearby tap may not be possible or inappropriate. Some pwMS find pressing on the lower abdomen helps. If all else fails regarding hesitancy intermittent self-catheterisation (ISC) may be the only option.

Frequency

In MS the commonest bladder problem is spasticity, or irritability, of the detrusor muscle. The detrusor can’t relax and this prevents the bladder filling to its maximum capacity. Frequent spasms of the detrusor muscle tell the brain that it is full and you need to go to the toilet. This causes frequency; i.e. the need to go to the toilet many times during the day and night. Frequency often goes with the symptom of urgency, the need to get to the toilet as quickly as possible to prevent yourself from being incontinent. Incontinence occurs as you often lose the ability to suppress or ignore the signals from the detrusor muscle and the sphincter relaxes or opens as part of spinal cord reflex. We typically treat this problem with the so-called anti-cholinergic drugs, for example, oxybutynin, solifenacin or tolterodine. The older generation anticholinergics such as oxybutynin cross the blood-brain-barrier and enter the brain where they can exacerbate cognitive problems in pwMS. This is why I avoid using them. The commonest side-effect of anticholinergics is dryness of the mouth and they can make constipation worse. There is also a risk that they will relax the bladder too much and precipitate urinary retention. All pwMS must be warned about this problem when starting anticholinergics; I have several pwMS under my care go into retention on starting anticholinergics.

The good news is that we now have a new muscle relaxant mirabegron (Betmiga), which works by activating the β3 adrenergic receptor in the detrusor muscle. I increasingly using it to avoid the side effects associated with the anticholinergics.

Urgency

When urgency is a problem try some distraction techniques such as breathing exercises and mental tricks (for example, counting) to take your mind off the bladder may be helpful. If urinary frequency is your main problem you may want to try and retrain your bladder by holding on for as long as you can each time before passing urine. The aim is to train the detrusor muscle to expand more so that it can hold on for longer when you need to go to the toilet. In my experience these behavioural techniques rarely work for long; MS is a relapsing and/or progressive disease and in all likelihood, the bladder pathways will be affected more due to the development of new lesions or the expansion of old lesions.

If you fail to respond to anticholinergics and/or mirabegron and behavioural techniques you need to have your bladder scanned to see if you have a raised residual volume. The residual volume is the amount of urine left behind after you have emptied your bladder. If the residual volume is greater than 80-100mL you may need to consider intermittent self-catheterisation or ISC. ISC serves two purposes; it increases your so-called functional residual bladder volume allowing more storage space for urine in the bladder; this reduces frequency and urgency. This is can help you if you have to take a long trip or to get through a social activity without having to pass urine. It also helps reduce nocturia or having to get up frequently at night to pass urine. You will be surprised how much better you feel if you get a good nights sleep. Reducing nocturia and improving sleep and improves daytime fatigue.

Another treatment that is becoming increasingly common is botox of the detrusor muscle. This paralyses the muscle turning it into a flaccid bag for urine storage. Almost all pwMS who have detrusor botox are using ISC. In the past, before botox was available, there were surgical techniques that could be used to denervate or remove the nerve supply to the bladder that had the same effect; these techniques are rarely used nowadays.

ISC also removes urine from the bladder. This is important if you are having recurrent bladder infections. The residual urine acts as a culture medium for bacteria and by clearing your bladder you can prevent bladder infections. The opposite can occur. If you are don’t get the ISC technique correct you can introduce bacteria into the bladder that then cause infections.

UTIs and disease progression

The more infections you have, in particular, severe infections, the more likely it is your MS will progress. Therefore if you have recurrent bladder infections you should try and prevent them occurring. How do you do this? Drink lots of liquids; flushing the bladder reduces infection rates. Also alkalinizing your urine by drinking citric acid (citrasoda or lemonade) also helps. Cranberry extract contains proanthocyanidins substance that reduces bacteria from colonising the bladder may help. Please note you need to use the extract and not the juice as the proanthocyanidin concentration in the juice is too low to have an effect.

An infrequently used option is bladder installation with a liquid containing sodium hyaluronate (Cystistat), which replaces the glycosaminoglycan (GAG) layer or glycocalyx of the bladder wall. This makes it difficult for bacteria to stick to the wall to cause infections and is one way of preventing bacterial biofilms, or slime, from forming. Biofilms are increasingly being recognised as a major problem as they prevent antibiotics reaching the bacteria to kill them and act as a nidus for recurrent infections. I have a few patients who have used Cystistat with dramatic results.

Increasing the frequency of ISC may also help reduce recurrent UTIs. Finally using urinary antiseptics may help reduce infection rates. Urinary antiseptics are antibiotics that are concentrated in the urine; they are given in low concentrations so they have little impact on the rest of the body. I tend to cycle their use, every 3-4 months, to prevent the bacteria in the bladder becoming resistant to a specific antibacterial. The agents I use currently are trimethoprim, cephalexin, nalidixic acid and nitrofurantoin.

Nocturia

If nocturia is your main problem using agents to concentrate the urine at night might help. There is a hormone called DDAVP that works on the kidney to reduce it making urine. You can take DDAVP as a nasal spray or tablets. DDAVP can only be taken once a day; if you use it continuously your kidneys will retain water and that can be very dangerous. The latter is called water intoxication; it presents as swelling of the feet and reduces the salt or sodium levels in your blood. If blood sodium level becomes too low it can cause problems. This is why when you start using DDAVP you need to have your sodium levels checked about 4-6 weeks after starting therapy. I am not sure why, but some neurologists are reluctant to prescribe DDAVP. This is a shame as it is a very good drug and can make the difference between getting a good nights sleep or waking feeling tired. You can use DDAVP intermittently and you can use it the day, for example when you need to go on a long trip or for social occasions, e.g. going to the movies or theatre. You can only use DDAVP once a day. The most common side effect is swelling of the feet; it happens in approximately a third of pwMS and is more common in pwMS who are less mobile.

Other advice I give to pwMS is that if you are a smoker then stopping smoking may significantly improve your bladder symptoms; nicotine irritates the bladder. Similarly, reducing alcohol and caffeine consumption may also help; both these agents affect the kidneys and cause them to make more urine. Medically this is referred to as diuresis; both nicotine and caffeine are diuretics. Try to anticipate times when urinary frequency and urgency are likely to be most inconvenient; reducing the amount that you drink beforehand may help. For example, when you go out, don’t drink much for 2-3 hours before you go out. However, do not reduce your total fluid intake to less than 1.5 litres each day. After you have finished passing urine, go back to the toilet again after a few minutes to try to pass some more urine. This is called the double micturition technique, which aims to make sure the bladder is emptied completely.

Conclusion

Finally, if all else fails some pwMS may need to be permanently catheterised. This can be done via the urethra or the lower abdominal wall. The latter is called a suprapubic catheter. Being permanently catheterised sounds awful, but in some pwMS, this drastically improves their quality of life. I have several pwMS who have let bladder dysfunction control their lives and as a result they have become socially isolated. They are typically anxious about being incontinent in public. To avoid this possibility they choose to stay at home. This is clearly unnecessary and with the strategies highlighted above adequate bladder control should be the norm in MS.

In my experience, the biggest hurdle to achieving adequate bladder control is pwMS accepting their bladder symptoms as being part of the disease and living with them.

If you have problems tell your nurse or neurologist; they will be able to help you.

About the author

Gavin

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

32 comments

  • Thanks prof G, very detailed explanation. I really enjoyed 1st part about viruses/infections, exciting research.

    And for thoses with incontinece who tried it all and failed, incontinence pads are a great solution and very liberating…..

    • You can also get incontinence proof knickers these days, much along the lines of period proof underwear. I doubt they will cope with serious accidents, but as an additional measure of confidence will probably help vastly (no idea if they do a gent’s version, but probably worth a look)

      • I will add this to my post as part of an upgrade. Once I have collected enough feedback on these posts I will be transferring them to specific self-management site called MS-Selfie.

  • An excellent post, very helpful.

    May I ask two questions to help my understanding?

    1. So even being on a DMT, it is still necessary/useful to avoid infections?

    2. If a person has inactive progressive disease, could their MS be reactivated by viral infection, e.g. common cold?


    Regarding bladder issues – I have circa 2 decades of progressive MS, my problem is urgency with a marked case of what I believe is termed “latchkey bladder”? And it’s a good term. I do great until I’m at my front door with the key in my hand. At this point, Tena Lady is a great thing. I am going to try your suggestion of distraction. :o)

    • Re: “So even being on a DMT, it is still necessary/useful to avoid infections?”

      Yes, although the DMT may counteract the effects of the infection, the infection may still trigger relapses. Some of the data on infections was from the interferon-beta trials, where study subjects were on interferon beta.

    • Re: “If a person has inactive progressive disease, could their MS be reactivated by viral infection, e.g. common cold?”

      Yes, this can occur. Interestingly, a trial of a cytokine called gamma-interferon in MS was stopped because it triggered relapses. The most potent stimulus your immune system to produce gamma interferon is a viral infection, therefore, I have little doubt that even in inactive progressive disease infections may trigger new lesions to form or the reactivation of old lesions.

      • Do you see any mechanism by which the flu jab itself could trigger relapse, even though it’s not live virus? (And would no doubt be better than flu itself.)

        • The flu jab has been studied using MRI and has been shown not to increase disease activity. In fact, it is the only vaccine to have a robust evidence base behind it in relation to this question.

  • Thank you for this. But if symptoms of urgency particularly at night accompanied with typical UTI symptoms drastically improve with an antibiotic it is fair to say that an infection is playing a part. However because cultures often produce no growth which, having read and read around this topic and spoken to doctors, is a common problem what do you think about this particularly as mouse doctor’s post implies antibiotic overuse makes Ms worse?

    • Yes. Not all UTIs are positive on dipstix. Why? Because not all bacteria produce nitrate reductase. The latter enzyme allows bacteria to convert nitrite in the urine to nitrate, which they then use during anaerobic respiration. However, you should still have detectable white cells on dipstix to indicate that not all is well. Approximately 30% of UTIs are caused by bacteria that nitrate negative.

      Yes, you can get culture negative UITs, this typically occurs if you are antibiotics or urinary anti-septics; occasionally there are too few bacteria in the culture to be detected. The commonest problem is that the urine is not processed quickly enough and you get mixed cultures that are often interpreted as contaminants. There is a dogma in the field, that should have been eliminated by now, that UITs can only really be caused by one organism. There is now overwhelming evidence that mixed organisms can cause UITs, particularly in patients with catheters.

      Another cause of culture-negative UTIs is if the infection is caused by fungi or possibly L-forms of bacteria. The latter are bacteria that lack a cell wall, usually driven by certain antibiotics. It is debatable if L-forms are a problem, as they mainly a laboratory phenomenon.

      • Luckily my GP assesses on symptoms rather than culture.
        As an aside my local lab where samples go Frimley Park is notoriously awful always losing samples or not reporting what has been requested!!

        Question
        if you try a couple of antibiotics before finding an effective one how long would you as a neurologist prescribe the effective one? My neurologist has always prescribed for at least two weeks whereas gps try and offer the minimum of 5 days

        Question
        Do you have a problem with ciprofloxacin as an antibiotic?

        • Re: “Do you have a problem with ciprofloxacin as an antibiotic?”

          No, I don’t but ciprofloxacin can’t be used long-term as a urinary antiseptic because it is and other fluoroquinolones antibiotics are associated with tendinopathy/tendinitis and tendon rupture.

          • A walk-in clinic prescribed me Ciprofloxacin whilst I was taking Tizanidine. I refused to accept it, so now I have an emergency supply of antibiotics from my GP. I do my own dip stick tests. Much safer.

        • Re: “If you try a couple of antibiotics before finding an effective one how long would you as a neurologist prescribe the effective one? My neurologist has always prescribed for at least two weeks whereas gps try and offer a minimum of 5 days.”

          It is not about trial and error. Your urine should be sent off for microscopy, culture and sensitivity to find out which antibiotics the organism is sensitive to. This will allow your HCP to select the appropriate antibiotic. What normally happens is that you get started on drug x and it gets changed to drug y if the organism is resistant to drug x. For uncomplicated UTIs 5-7 days should be fine. If you a longer course it implies you are colonised.

          • It tends to be trial-and-error when cultures are negative so as a result the infection can take a while to treat as the effective antibiotic is not necessarily the first one offered hence the question as to how long an antibiotic would normally be offered for.

    • I am not sure of any evidence that antibiotic overuse per se makes MS worse. In comparison, we have some evidence that infections, particularly severe infections, make MS worse. Choose your poison?

  • Thank you Prof G – really interesting and useful! The asymptomatic infections that you describe (and also the asymptomatic E coli urinary infection I have had for at least 2 years) should these be tested for and treated? I was told by a hospital consultant (medical) that my asymptomatic UTI should NOT be treated, but is this the case when I also have progressive MS?
    Your discussions on symptom improvements for PwMS is very, very welcome. Thank you again.

    • Why do pwMS have an asymptomatic UTIs? Are they intermittently catheterizing or do they have an indwelling catheter? The main reason for this is that that are probably chronically colonised by bacteria, which may damage the glycocalyx that lines their bladder wall. If this is the case they could try alkalinization of the urine, D-mannose or cranberry extract. Sodium hyaluronate (Cystistat) is given as bladder irrigation and in all the patients I have used it they had indwelling catheters.

      Some urologists use monthly bladder washouts with a class of drug called aminoglycosides to get on top of the colonisation problem. This is usually reserved for patients with frequent, unscheduled or emergency, hospital admissions in an attempt to prevent them from needing hospital admissions.

  • After a decade of UTIs (I self cath three times daily) I started taking Hiprex (Methenamine Hippurate). I am told this drug doesn’t actually attack the bacteria but creates a hostile environment in which bacteria can’t live and they gradually die off. Hiprex has proved very successful for me, so has it been given enough consideration as a medication for UTIs? I am not even sure it’s an antibiotic strictly speaking – the urologist who advised me to take it said it was more like a disinfectant.

  • Is there the possibility that UTIs which test negative for bacteria would actually be better termed as interstitial cystitis?

  • ProfG I’m really delighted that you are doing the MS-Selfie posts!. It’s so great to have the clinicial and medical details as well as practical advice that we can try implementing as PwMS.

    I think your advice about relaxing to fully empty the bladder is correct and, for those interested, I’ve found using a yoga breath helps: breathe slowly through mouth making the letter R sound as you breathe in and the phonic of the letter H (huh) as you breathe out.

    I also use advice given to me years ago by two different gynecologists: when you’ve finished peeing wait a few seconds, then lean forward over your knees and try again. Before going to bed, go to the loo, then around 15mins later or so, go again. I’ve recommended this to friends who, like me, are shocked at how much more urine you can pass, even when you thought you’d properly been. Obviously the short while later works during the day too, when you can.

    Relate to the ‘latchkey’ urgency so will definitely try the distraction method you’re proposing.

  • Do you have any advice, especially in terms of self management, on mitigating any possible damage if a person with MS gets a cold virus? Just the obvious things – keep warm, take rest, eat healthily, plenty of fruit and veg?

  • I had no idea that betmiga was a newish drug.
    I have UTIs if I jog or run.
    I am sick of incontinence, it’s a dreadful part of life with MS

  • I may be wishful thinking but a high number of women get bladder issues in the general population – one in three. So this helps me be positive about my bladder i.e that it might not be my MS causing the problems.
    Apparently one in three women in the general population have adult incontinence of varying degrees.
    The urethra in women is 1.5 inches long and about 10 times shorter than mens and this is one reason why women get UTI’s. The bacteria have a much shorter distance to travel.

    Prof G, can you confirm this please? Thanks.

    • The ‘female incontinence’ you are referring to is stress incontinence and is not the same as that what occurs with a so-called MS or neurogenic bladder. However, women with MS can have both.

      • Thanks very much Prof G. I probably have stress incontinence as it is mainly when I am walking outside the house, the movement of me walking brings on the urgency and incontinence. If I was to stay at home or go from home to car and not walk much, I wouldn’t have much incontinence.

  • Excellent post, thank you !
    I wondered about controlling bladder spasms. I have stopped drinking tea, and eating toms and chocolate : ( and hope this will help me calm the spasms.
    The spasms are like when I have a UTI, painful… but no UTI comes up on the dipstick or at the lab sometimes.

    • All the drugs that reduce urinary frequency may increase the urinary residual volume that acts as a culture medium for bacteria and hence is a risk factor for UTIs. This is side effect s not unique to Betmiga. If you start these antispasmodics you need to make sure you are emptying your bladder appropriately.

    • Is this not a side effect simply because UTI is a reason why people have trouble with their bladders and end up being prescribed this drug so rather than causing the UTI betmiga is used by people who do get UTIs?

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